There is a significant current need to elucidate the molecular mechanisms of the side-effects caused by widely-used pharmaceuticals. Examples include the acute nephrotoxicity and irreversible ototoxicity promoted by the cationic drugs gentamicin and cisplatin. Gentamicin is an aminoglycoside antibiotic used for the prevention and treatment of life-threatening gram-negative bacterial infections, such as tuberculosis and meningitis. Cisplatin is used to treat a broad spectrum of cancers including head and neck, ovarian, cervical, stomach, bladder, sarcoma, lymphoma, testicular cancer and others. The objective of this study is to design and synthesize rhodamine derivatives that can be used for the construction of geometrically well-defined cationic drug conjugates. The long-term goal is to use the conjugates as tools to aid in elucidating the properties and identities of ion channels involved in the uptake of cationic pharmaceuticals into kidney and cochlear hair cells. This will shed light on the origin and potential prevention of unwanted side effects such as nephrotoxicity and ototoxicity associated with specific cationic drugs. A series of extended rhodamine analogs with reactive groups for biomolecule conjugation has been synthesized. These fluorophores show similar spectral properties to their prototype, Texas Red succinimidyl ester (TR-SE). However, they contain rigid linkers between the fluorophore and amine-reactive moiety. The resultant gentamicin conjugates of these materials are rigidified enabling one to assess channel pore dimensions without the confounding issue of conjugate folding. Preliminary cell studies are promising, as one observes reduced gentamicin uptake in both kidney and sensory hair cell upon systematically increasing the dimension of the fluorophore. This work has enabled us to tentatively assign the maximum dilated MET channel pore size as between 1.44 nm to 1.56 nm. However, this preliminary finding, though encouraging, needs further validation via ongoing studies with larger diameter fluorophore conjugates, A cisplatin-Texas Red conjugate has also been synthesized to enable studies of cellular uptake mechanisms. This conjugate preserves not only the spectral properties of Texas Red after conjugation, but also the cytotoxicity of cisplatin. This has been validated in zebrafish. The series of rhodamine probes that have been conjugated to gentamicin should be similarly useful for cisplatin studies. These studies are planned. Additional future work includes the synthesis of semi-flexible (glycol) and flexible (alkyl) linkers to evaluate structure-activity relationships.

This dissertation examines how to evaluate a place-based poverty reduction program across different sites and scales. Unpacking urban planning’s dominant, normative construction of poverty, neighbourhoods, youth, and evaluation, this thesis presents an alternative view of evaluation, which recognizes the complexity and diversity of qualitative narratives describing the impacts of targeted human service programs on the places and peoples they serve. To answer this question, I crafted a theoretical framework linking the concept of the right to the city as presented by Lefebvre (1996), to Uri Bronfenbrenner’s (1977, 1979), 1995) understanding of the micro, macro, and meso systems in which children and youth operate. I then conducted a small-scale, qualitative case study of Pathways to Education Canada as it replicated and expanded, to examine and explore different ways of evaluating the success of a place-based poverty human service program. Using a participatory methodology, I listened to different stakeholders’ voices, particularly those of youth and staff, to examine and explore tensions in the construction of success.

This dissertation examines how to evaluate a place-based poverty reduction program across different sites and scales. Unpacking urban planning’s dominant, normative construction of poverty, neighbourhoods, youth, and evaluation, this thesis presents an alternative view of evaluation, which recognizes the complexity and diversity of qualitative narratives describing the impacts of targeted human service programs on the places and peoples they serve. To answer this question, I crafted a theoretical framework linking the concept of the right to the city as presented by Lefebvre (1996), to Uri Bronfenbrenner’s (1977, 1979), 1995) understanding of the micro, macro, and meso systems in which children and youth operate. I then conducted a small-scale, qualitative case study of Pathways to Education Canada as it replicated and expanded, to examine and explore different ways of evaluating the success of a place-based poverty human service program. Using a participatory methodology, I listened to different stakeholders’ voices, particularly those of youth and staff, to examine and explore tensions in the construction of success.

During the past several decades, earthquakes have caused extensive damage to buildings, including wood-frame, single-family dwellings, in the United States. In order to mitigate future losses, existing buildings in earthquake prone areas should be evaluated for their seismic safety. This is also an important issue for buildings in Oregon due to the Cascadia subduction zone along its west coast. One seismically vulnerable element observed in wood-frame, single-family dwellings is the shear walls. In general, assessment of shear wall seismic performance can be accomplished by a building-specific engineering calculation. Extra effort is required if the effects of plan irregularity are a concern. This project aims to facilitate seismic evaluation of wood-frame dwellings by proposing a new engineering-based rapid visual screening method to examine the expected performance level of the structure's exterior shear walls to resist lateral forces from ground motions, including torsional forces induced from plan irregularity. In order to achieve the objective, SAPWood software was used to perform a series of nonlinear time-history analyses for 480 representative models, covering different combinations of shape parameters and shear wall opening-related parameters. The evolutionary parameter hysteresis model was used to represent the load-displacement relationship of structural panel-sheathed shear walls and a ten parameter CUREE hysteresis model for gypsum wallboard sheathed walls. The calculated maximum lateral drifts were used as basic information for the development of the new method. Through the development process, the significance of both plan configuration and shear wall openings were emphasized as they affect the overall seismic performance of a building through building mass, lateral stiffnesses, and eccentricities. Within the study range, single-family dwellings with two stories, a larger percentage of openings, and having a garage door were shown to be more vulnerable to seismic events. Plan configuration and shear wall openings were important features especially in houses located in high 1 (0.5g ≤ S[subscript a] < 1.0g) and high 2 (1.0g ≤ S[subscript a] < 1.5g) seismicity regions, as they could potentially lead to severe damage. For low and moderate seismicity, the performance ranges from satisfying the collapse prevention limit to the immediate occupancy limit. The developed piRVS (plan irregularity Rapid Visual Screening) takes into consideration the shape of the floor plan, number of stories, base rectangular area, percent cutoff, and openings from doors/windows and garage doors, and supports evaluation at the immediate occupancy (IO), life safety (LS), and collapse prevention (CP) performance levels. The piRVS provides relatively more conservative assessment results than FEMA 154 and ASCE 31 Tier 1. Its prediction for the two applicable Northridge earthquake damage samples is reasonable. This method will help architects, engineers, building officials, and trained inspectors in examining the expected seismic performance of shear walls, considering the effects of plan irregularity in wood-frame, single-family dwellings / Graduation date: 2012

No description available.

L’objectif de cette thèse était d’évaluer Espace de Transition (ET), un programme novateur d’intervention par les arts de la scène visant à favoriser la réadaptation psychosociale d’adolescents et de jeunes adultes présentant des troubles mentaux stabilisés et à diminuer la stigmatisation des individus aux prises avec des problèmes de santé mentale. Ce programme a été conçu par une équipe de cliniciens du département de psychiatrie du Centre hospitalier universitaire Ste-Justine, en collaboration avec des artistes professionnels, et est livré depuis le printemps 2009. L’évaluation du programme ET a été conduite de manière indépendante, selon des approches collaborative et naturaliste et en usant de méthodes mixtes. Les données de recherche ont été recueillies avant pendant et après le programme auprès de l’ensemble des participants à deux sessions distinctes (N = 24), de même qu’auprès des deux artistes instructeurs, de la psychoéducatrice responsable du soutien clinique, ainsi que des psychiatres et autres intervenants ayant référé des participants (N=11). Des entrevues semi-structurées individuelles et de groupe, des observations directes et des questionnaires ont servi à recueillir les données nécessaires à l’évaluation. Des analyses quantitatives de variance, ainsi que des analyses qualitatives thématiques ont été réalisées et leurs résultats ont été interprétés de manière intégrée. Le premier chapitre empirique de la thèse relate l’évaluation de la mise en œuvre du programme ET. Cette étude a permis de constater que le programme avait rejoint des participants correspondant de près à la population visée et que ceux-ci présentaient globalement des niveaux élevés d’assiduité, d’engagement et d’appréciation du programme. L’évaluation de la mise en œuvre a en outre permis de conclure que la plupart des composantes du programme identifiées a priori comme ses paramètres essentiels ont été livrées tel que prévu par les concepteurs et que la plupart d’entre elles ont été largement appréciées et jugées pertinentes par les participants et les autres répondants consultés. Le second chapitre empirique consiste en un article portant sur l’évaluation des effets du programme ET relativement à l’atteinte de trois de ses objectifs intermédiaires, soient l’amélioration 1) du fonctionnement global, 2) du confort relationnel et des compétences sociales, ainsi que 3) de la perception de soi des participants présentant des troubles mentaux. Les résultats de cette étude ont révélé des changements significatifs et positifs dans le fonctionnement global des participants suite au programme, tel qu’évalué par les cliniciens référents et partiellement corroboré par les participants eux-mêmes. Des améliorations en ce qui concerne le confort relationnel, les compétences sociales et la perception de soi ont également été objectivées chez une proportion substantielle de participants, bien que celles-ci ne se soient pas traduites en des différences significatives décelées par les analyses quantitatives de groupe. Le troisième et dernier chapitre empirique de la thèse relate une étude exploratoire des mécanismes sous-tendant les effets du programme ET ayant conduit à l’élaboration inductive d’une théorie d’action de ce programme. Cette investigation qualitative a révélé quatre catégories de mécanismes, soient des processus de 1) gain d’expérience et de gratification sociales, 2) de désensibilisation par exposition graduelle, 3) de succès et de valorisation, et 4) de normalisation. Cette étude a également permis de suggérer les caractéristiques et composantes du programme qui favorisent la mise en place ou l’impact de ces mécanismes, tels l’environnement et l’animation non cliniques du programme, la composition hétérogène des groupes de participants, le recours aux arts de la scène, ainsi que la poursuite d’une réalisation collective et son partage avec un public extérieur au programme. Globalement, les études présentées dans la thèse appuient la pertinence et le caractère prometteur du programme ET, tout en suggérant des pistes d’amélioration potentielle pour ses versions ultérieures. Par extension, la thèse soutient l’efficacité potentielle d’interventions réadaptatives mettant en œuvre des composantes apparentées à celles du programme ET pour soutenir le rétablissement des jeunes aux prises avec des troubles mentaux. / The objective of this thesis was to evaluate Espace de Transition (ET), an innovative art-based program aimed at fostering the rehabilitation of adolescents and young adults with recently stabilized psychiatric disorders and diminishing the stigmatization experienced by individuals with mental health problems. This program was designed by a team of clinicians from Ste-Justine Hospital’s psychiatry unit, in collaboration with professional artists. It is delivered since the spring of 2009. The evaluation of program ET was conducted in an independent yet collaborative manner, using a naturalistic approach and mixed methods. Data were collected before, during, and after the program from all participants who took part in two distinct sessions (N = 24), as well as from the two artist instructors, the psychoeducator who provided clinical support during the workshops, and the clinicians who referred participants (N=11). Individual and group semi-structured interviews, direct observations, and questionnaires served to collect the necessary data. Quantitative analyses of variance and qualitative thematic analyses were conducted and their results were interpreted in an integrated manner. The first empirical chapter of the thesis reports on the evaluation of the implementation of program ET. This evaluation showed that the program reached participants closely corresponding to its targeted population and that these youths globally presented elevated levels of assiduity, engagement in, and appreciation of the program. This evaluation also allowed to conclude that most essential program components were delivered as intended by designers and were largely appreciated and judged pertinent by participants and other respondents. The second empirical chapter presents an article detailing the evaluation of the effects of the program ET. This evaluation focused on three of its intermediate objectives: the improvement of 1) global functioning, 2) social comfort and competence, and 3) self-perception in program participants suffering from mental disorders. Results of this study revealed significant and positive changes in the global functioning of participants following the program, as assessed by their referring clinicians and partially corroborated by participants themselves. Improvements in social comfort and competence and self-perception were also noted in a substantial proportion of participants, although they did not translate in significant differences detected by group-level quantitative analyses. The third and last empirical chapter of the thesis reports on a study which sought to explore the mechanisms underlying the effects of program ET and to inductively elaborate a theory of action of the program. This qualitative investigation revealed four categories of mechanisms: 1) social experience and gratification, 2) desensitization by gradual exposure, 3) success and valorization, and 4) normalization. This study also allowed to identify program characteristics and components that seemed to favor the onset or impact of these mechanisms, such as the non-clinical setting and conducting of the program, the heterogeneous composition of the groups, the use of performing arts, and the pursuit of a collectively achieved artistic product and its presentation to an external public. Globally, the studies presented in the thesis support the relevance and promising character of program ET, while suggesting potential improvements for future versions. By extension, the thesis supports the potential efficacy of rehabilitation strategies which include components analogous to those of ET in fostering the recovery of youths with mental disorders.

A glicação é uma reação não enzimática que ocorre entre proteínas e açúcares redutores e, é responsável pela formação de adultos e de ligações cruzadas entre proteínas, como por exemplo: a pentosidina, produto final de glicação avançada que se acumula em vários tecidos ao longo do tempo. A glicação é deletéria para o organismo e está associada a modificações estruturais em proteínas e alterações de suas funções específicas, tais como: atividade enzimática, capacidade de ligação e tempo de vida de proteínas, além de ser responsável pela produção de espécies reativas de oxigênio (EROS). O mecanismo de formação da pentosidina envolve reações oxidativas e, uma das estratégias para minimizá-Ia é o aumento da atividade antioxidante nos tecidos. A pariparoba (Pothomorphe umbellata (L.) Miq) demonstrou atividade antioxidante in vitro e in vivo quando aplicada sobre a pele. Essa atividade foi atribuída ao 4-nerolidilcatecol (4-NC), que se mostrou 10 vezes mais potente que o &#945;-tocoferol. Os extratos de pariparoba também inibiram a lipoperoxidação espontânea da pele em camundongos sem pelo. Neste trabalho empregou-se o modelo de glicação de albumina de soro bovino (BSA) frente à D-ribose, com avaliação da fluorescência produzida pela pentosidina formada na reação. Avaliou-se igualmente a atividade do 4-NC em diferentes concentrações sobre a reação de glicação da BSA em presença de D-ribose após 24 horas, empregando-se a aminoguanidina como controle positivo. Nas condições experimentais o 4-NC não foi capaz de inibir a reação de glicação, ao contrário da aminoguanidina. Foi também utilizado modelo para avaliação da propriedade contrátil de fibroblastos em matriz tridimensional de gel de colágeno, glicado e não glicado com D-ribose. O 4-NC na concentração de 100 &#181;M permitiu a manutenção da propriedade contrátil de fibroblastos em gel colágeno glicado. Estudos de glicação em maiores períodos de tempo devem ser realizados visando a confirmar a possível atividade anti-glicação deste composto. / Glycation is a non enzymatic reaction which occurs between proteins and reductor sugars, responsible for the formation of adducts and crosslinkers between proteins, such as, pentosidine, an advanced glycation end-product (AGE) which accumulates in many tissues during aging. AGEs accumulation is deleterious to the body and is associated with structural modifications in proteins and imbalance in their specific functions, such as: enzymatic activity, binding capacity, protein turnover and also responsible for the production of reactive oxygen species (ROS). The mechanism of pentosidine formation involves oxidative reactions. One of the strategies to reduce pentosidine formation is by increasing antioxidant activity in tissues. Pariparoba (Pothomorphe umbellata (L.) Miq. has showed antioxidant activity in vitro and in vivo when applied on the skin. This activity was attributed to 4-nerolydilcatechol (4-NC), which is 10 times more potent than &#945;-tocopherol. Extracts of Pariparoba also inhibited the spontaneous lipid peroxidation in the skin of hairless mice. In this work, the bovine serum albumin (BSA) model for glycation with D-ribose, evaluated by pentosidine fluorescence spectroscopy was employed. The activity of 4¬NC was evaluated in different concentrations in this model after 24 hours. Aminoguanidine was used as positive control. In this experimental condition, 4-NC was not capable to inhibit the BSA glycation. We also evaluated the contractile properties of fibroblasts on tridimensional matriz of collagen gel glycated or not with D-ribose. 4-NC (100 &#181;M) was able to keep the contractile capacity of fibroblasts in glycated collagen. Studies of glycation in longer periods of time should be made in order to further evaluate the possible anti-glycation activity of this compound.

L’objectif de cette thèse était d’évaluer Espace de Transition (ET), un programme novateur d’intervention par les arts de la scène visant à favoriser la réadaptation psychosociale d’adolescents et de jeunes adultes présentant des troubles mentaux stabilisés et à diminuer la stigmatisation des individus aux prises avec des problèmes de santé mentale. Ce programme a été conçu par une équipe de cliniciens du département de psychiatrie du Centre hospitalier universitaire Ste-Justine, en collaboration avec des artistes professionnels, et est livré depuis le printemps 2009. L’évaluation du programme ET a été conduite de manière indépendante, selon des approches collaborative et naturaliste et en usant de méthodes mixtes. Les données de recherche ont été recueillies avant pendant et après le programme auprès de l’ensemble des participants à deux sessions distinctes (N = 24), de même qu’auprès des deux artistes instructeurs, de la psychoéducatrice responsable du soutien clinique, ainsi que des psychiatres et autres intervenants ayant référé des participants (N=11). Des entrevues semi-structurées individuelles et de groupe, des observations directes et des questionnaires ont servi à recueillir les données nécessaires à l’évaluation. Des analyses quantitatives de variance, ainsi que des analyses qualitatives thématiques ont été réalisées et leurs résultats ont été interprétés de manière intégrée. Le premier chapitre empirique de la thèse relate l’évaluation de la mise en œuvre du programme ET. Cette étude a permis de constater que le programme avait rejoint des participants correspondant de près à la population visée et que ceux-ci présentaient globalement des niveaux élevés d’assiduité, d’engagement et d’appréciation du programme. L’évaluation de la mise en œuvre a en outre permis de conclure que la plupart des composantes du programme identifiées a priori comme ses paramètres essentiels ont été livrées tel que prévu par les concepteurs et que la plupart d’entre elles ont été largement appréciées et jugées pertinentes par les participants et les autres répondants consultés. Le second chapitre empirique consiste en un article portant sur l’évaluation des effets du programme ET relativement à l’atteinte de trois de ses objectifs intermédiaires, soient l’amélioration 1) du fonctionnement global, 2) du confort relationnel et des compétences sociales, ainsi que 3) de la perception de soi des participants présentant des troubles mentaux. Les résultats de cette étude ont révélé des changements significatifs et positifs dans le fonctionnement global des participants suite au programme, tel qu’évalué par les cliniciens référents et partiellement corroboré par les participants eux-mêmes. Des améliorations en ce qui concerne le confort relationnel, les compétences sociales et la perception de soi ont également été objectivées chez une proportion substantielle de participants, bien que celles-ci ne se soient pas traduites en des différences significatives décelées par les analyses quantitatives de groupe. Le troisième et dernier chapitre empirique de la thèse relate une étude exploratoire des mécanismes sous-tendant les effets du programme ET ayant conduit à l’élaboration inductive d’une théorie d’action de ce programme. Cette investigation qualitative a révélé quatre catégories de mécanismes, soient des processus de 1) gain d’expérience et de gratification sociales, 2) de désensibilisation par exposition graduelle, 3) de succès et de valorisation, et 4) de normalisation. Cette étude a également permis de suggérer les caractéristiques et composantes du programme qui favorisent la mise en place ou l’impact de ces mécanismes, tels l’environnement et l’animation non cliniques du programme, la composition hétérogène des groupes de participants, le recours aux arts de la scène, ainsi que la poursuite d’une réalisation collective et son partage avec un public extérieur au programme. Globalement, les études présentées dans la thèse appuient la pertinence et le caractère prometteur du programme ET, tout en suggérant des pistes d’amélioration potentielle pour ses versions ultérieures. Par extension, la thèse soutient l’efficacité potentielle d’interventions réadaptatives mettant en œuvre des composantes apparentées à celles du programme ET pour soutenir le rétablissement des jeunes aux prises avec des troubles mentaux. / The objective of this thesis was to evaluate Espace de Transition (ET), an innovative art-based program aimed at fostering the rehabilitation of adolescents and young adults with recently stabilized psychiatric disorders and diminishing the stigmatization experienced by individuals with mental health problems. This program was designed by a team of clinicians from Ste-Justine Hospital’s psychiatry unit, in collaboration with professional artists. It is delivered since the spring of 2009. The evaluation of program ET was conducted in an independent yet collaborative manner, using a naturalistic approach and mixed methods. Data were collected before, during, and after the program from all participants who took part in two distinct sessions (N = 24), as well as from the two artist instructors, the psychoeducator who provided clinical support during the workshops, and the clinicians who referred participants (N=11). Individual and group semi-structured interviews, direct observations, and questionnaires served to collect the necessary data. Quantitative analyses of variance and qualitative thematic analyses were conducted and their results were interpreted in an integrated manner. The first empirical chapter of the thesis reports on the evaluation of the implementation of program ET. This evaluation showed that the program reached participants closely corresponding to its targeted population and that these youths globally presented elevated levels of assiduity, engagement in, and appreciation of the program. This evaluation also allowed to conclude that most essential program components were delivered as intended by designers and were largely appreciated and judged pertinent by participants and other respondents. The second empirical chapter presents an article detailing the evaluation of the effects of the program ET. This evaluation focused on three of its intermediate objectives: the improvement of 1) global functioning, 2) social comfort and competence, and 3) self-perception in program participants suffering from mental disorders. Results of this study revealed significant and positive changes in the global functioning of participants following the program, as assessed by their referring clinicians and partially corroborated by participants themselves. Improvements in social comfort and competence and self-perception were also noted in a substantial proportion of participants, although they did not translate in significant differences detected by group-level quantitative analyses. The third and last empirical chapter of the thesis reports on a study which sought to explore the mechanisms underlying the effects of program ET and to inductively elaborate a theory of action of the program. This qualitative investigation revealed four categories of mechanisms: 1) social experience and gratification, 2) desensitization by gradual exposure, 3) success and valorization, and 4) normalization. This study also allowed to identify program characteristics and components that seemed to favor the onset or impact of these mechanisms, such as the non-clinical setting and conducting of the program, the heterogeneous composition of the groups, the use of performing arts, and the pursuit of a collectively achieved artistic product and its presentation to an external public. Globally, the studies presented in the thesis support the relevance and promising character of program ET, while suggesting potential improvements for future versions. By extension, the thesis supports the potential efficacy of rehabilitation strategies which include components analogous to those of ET in fostering the recovery of youths with mental disorders.

A glicação é uma reação não enzimática que ocorre entre proteínas e açúcares redutores e, é responsável pela formação de adultos e de ligações cruzadas entre proteínas, como por exemplo: a pentosidina, produto final de glicação avançada que se acumula em vários tecidos ao longo do tempo. A glicação é deletéria para o organismo e está associada a modificações estruturais em proteínas e alterações de suas funções específicas, tais como: atividade enzimática, capacidade de ligação e tempo de vida de proteínas, além de ser responsável pela produção de espécies reativas de oxigênio (EROS). O mecanismo de formação da pentosidina envolve reações oxidativas e, uma das estratégias para minimizá-Ia é o aumento da atividade antioxidante nos tecidos. A pariparoba (Pothomorphe umbellata (L.) Miq) demonstrou atividade antioxidante in vitro e in vivo quando aplicada sobre a pele. Essa atividade foi atribuída ao 4-nerolidilcatecol (4-NC), que se mostrou 10 vezes mais potente que o &#945;-tocoferol. Os extratos de pariparoba também inibiram a lipoperoxidação espontânea da pele em camundongos sem pelo. Neste trabalho empregou-se o modelo de glicação de albumina de soro bovino (BSA) frente à D-ribose, com avaliação da fluorescência produzida pela pentosidina formada na reação. Avaliou-se igualmente a atividade do 4-NC em diferentes concentrações sobre a reação de glicação da BSA em presença de D-ribose após 24 horas, empregando-se a aminoguanidina como controle positivo. Nas condições experimentais o 4-NC não foi capaz de inibir a reação de glicação, ao contrário da aminoguanidina. Foi também utilizado modelo para avaliação da propriedade contrátil de fibroblastos em matriz tridimensional de gel de colágeno, glicado e não glicado com D-ribose. O 4-NC na concentração de 100 &#181;M permitiu a manutenção da propriedade contrátil de fibroblastos em gel colágeno glicado. Estudos de glicação em maiores períodos de tempo devem ser realizados visando a confirmar a possível atividade anti-glicação deste composto. / Glycation is a non enzymatic reaction which occurs between proteins and reductor sugars, responsible for the formation of adducts and crosslinkers between proteins, such as, pentosidine, an advanced glycation end-product (AGE) which accumulates in many tissues during aging. AGEs accumulation is deleterious to the body and is associated with structural modifications in proteins and imbalance in their specific functions, such as: enzymatic activity, binding capacity, protein turnover and also responsible for the production of reactive oxygen species (ROS). The mechanism of pentosidine formation involves oxidative reactions. One of the strategies to reduce pentosidine formation is by increasing antioxidant activity in tissues. Pariparoba (Pothomorphe umbellata (L.) Miq. has showed antioxidant activity in vitro and in vivo when applied on the skin. This activity was attributed to 4-nerolydilcatechol (4-NC), which is 10 times more potent than &#945;-tocopherol. Extracts of Pariparoba also inhibited the spontaneous lipid peroxidation in the skin of hairless mice. In this work, the bovine serum albumin (BSA) model for glycation with D-ribose, evaluated by pentosidine fluorescence spectroscopy was employed. The activity of 4¬NC was evaluated in different concentrations in this model after 24 hours. Aminoguanidine was used as positive control. In this experimental condition, 4-NC was not capable to inhibit the BSA glycation. We also evaluated the contractile properties of fibroblasts on tridimensional matriz of collagen gel glycated or not with D-ribose. 4-NC (100 &#181;M) was able to keep the contractile capacity of fibroblasts in glycated collagen. Studies of glycation in longer periods of time should be made in order to further evaluate the possible anti-glycation activity of this compound.

Die Dissertation beschreibt am Beispiel einer Längsschnittstudie in der Papierindustrie, wie Effekte von Maßnahmen der betrieblichen Gesundheitsförderung in geschätzten ökonomischen Nutzen übertragen werden können. Ausgangspunkt der Untersuchung ist das Variablen-Modell nach Locke und Latham (1990). Darauf aufbauend wurden geeignete Indikatoren und Messinstrumente ausgewählt und in mehreren Voruntersuchungen überprüft. Hauptinstrument ist ein Fragebogen, der im quasiexperimentellen Design zur Ist-Analyse und nach Umsetzung der Maßnahmen eingesetzt wurde. An der ersten Befragung im Oktober 2000 nahmen 320 Gewerbliche und Angestellte des Unternehmens (Rücklauf 89%), an der zweiten drei Jahre später 402 Mitarbeiter (Rücklauf 91%) teil. Für den Längsschnitt standen die Fragebögen von 118 Mitarbeitern zur Verfügung. Neben den Fragebogendaten wurden personbezogene Daten zum Krankenstand erhoben, die auf freiwilliger Basis mit den Fragebogendaten verknüpft wurden, worauf sich 71% der im Jahr 2000 Befragten und 80% der im Jahr 2003 Befragten einlassen konnten. Zur Absicherung der Validität kamen weitere Untersuchungsmethoden zum Einsatz: für 19 Tätigkeiten wurde eine objektive arbeitspsychologische Tätigkeitsanalyse (Pohlandt, Schulze, Jordan &amp;amp; Richter, 2002) durchgeführt, die beteiligten Bereiche wurden in einem Rankingverfahren durch betriebliche Experten eingeschätzt, die organisationale Einbindung der betrieblichen Gesundheitsförderung wurde zu beiden Untersuchungszeitpunkten mit Hilfe des Fragebogens von Breucker (Prävention online, 2000) erfasst, es fanden 22 strukturierte Interviews mit den Beschäftigten zur Einschätzung der durchgeführten Maßnahmen statt. Die Ergebnisse der ersten Mitarbeiterbefragung wurden zurückgemeldet, diskutiert und zu 12 Maßnahmen verdichtet. Diese 12 Maßnahmen wurden in die Zweitbefragung mit aufgenommen, wobei die aktive Beteiligung an ihnen und die Zufriedenheit mit ihrer Umsetzung eingeschätzt werden sollten. Zur Ermittlung der Effizienz wurden eine erweiterte Kosten-Nutzen-Analyse (nach Schmidt, Hunter &amp;amp; Pearlman, 1982) und eine Kosten-Nutzwert-Analyse (nach Rinza &amp;amp; Schmitz, 1992) durchgeführt. Fast alle im Fragebogen erfassten Variablen hatten sich zwischen der ersten und zweiten Befragung signifikant verbessert (Arbeitsintensität, Tätigkeitsspielraum, Motivationspotenzial der Tätigkeit, soziale Unterstützung, sozialen Stressoren, Commitment, Arbeitszufriedenheit, allgemeines Befinden, psychosomatische Beschwerden). Nicht signifikant waren die Änderungen beim (multimodal beeinflussten) Krankenstand, sowie bei der Einschätzung der Führung. Bezüglich der Effektstärke konnte bei 9 der 12 Maßnahmen mindestens ein positiver Unterscheidungseffekt aufgezeigt werden. Bei der Ermittlung des (subjektiv erlebten) Nutzwertes der Maßnahmen kamen alle 12 Maßnahmen in den positiven Bereich. Mit der Kosten-Nutzen-Analyse wurde ein positives Kosten-Nutzen-Verhältnis für 6 der 9 verbleibenden Maßnahmen (zwischen 1:71 und 1:1,5) ermittelt. Diese Ergebnisse wurden kritisch hinterfragt und durch Einbeziehung von Diskontierung, spezifischen Effizienzkriterien, Sensitivitätsanalysen und Worst-Case-Berechnung relativiert (vgl. Anforderungen nach Drummond, O´Brien, Stoddart &amp;amp; Torrance, 1987/1997). Im Vergleich zur Kosten-Nutzen-Analyse wurden bei der Kosten-Nutzwert-Analyse deutlich andere Rangreihen ermittelt. Die kritische Gesamtschau der Ergebnisse ermöglicht spezifische Empfehlungen für fünf Maßnahmengruppen. Es zeigte sich, dass die gemeinsame Erörterung von Kosten-Nutzen-Analyse und Nutzwert zusätzliche und bisher nicht erfasste Aspekte beim Umgang mit den Maßnahmen eröffnet. / The thesis illustrates a longitudinal study in the paper industry. It shows how effects resulting from measures of occupational health promotion may be translated into an estimated economic advantage. The starting point of the study is the high performance cycle (Locke &amp;amp; Latham: 1990). Proceeding from that, appropriate indicators and measuring instruments were selected and tested in several pre-studies. The main instrument is a questionnaire, used in a comparative design before and after the translation of the measures into practice. 320 white- and blue-collar workers took part in the first survey in October 2000 (response rate 89%), whereas 402 workers participated in the second survey which was conducted three years later (response rate 91%). After all, complete data sets for the longitudinal analysis were available from 118 participants. Apart from that personal data concerning absenteeism were used, which were then connected to the questionnaire data on a voluntary basis. Whereas in 2000, in the first survey, 71% of the participants agreed to the connection of their personal data with the questionnaire, 80% agreed to it in the second survey, in 2003. To guarantee the questionnaire?s validity an array of additional methods was used: an objective occupational job analysis (Pohlandt, Schulze, Jordan &amp;amp; Richter, 2002) of 19 different occupations was carried out and the company?s experts evaluated the branches involved by ranking. Furthermore the organizational embedding of occupational health promotion measures was investigated in both surveys with the help of Breucker?s questionnaire (Prevention online, 2000) and additionally 22 structured interviews with the employees took place in order to evaluate the acceptance of the measures conducted. The results of the first employee survey were reported back, discussed and condensed into 12 measures. These 12 measures were then included in the second survey when the employees? active participation in the measures? implementation and their satisfaction with the measures? effects should be evaluated. To determine the measures? actual efficiency an extended cost-benefit-analysis (with reference to Schmidt, Hunter &amp;amp; Pearlman: 1982) and a cost-utility-analysis (with reference to Rinza &amp;amp; Schmitz: 1992) were conducted. Nearly all variables investigated in the questionnaire had significantly improved between the first and the second survey (indicators of job demands, occupational scope, motivational potential of occupation, social support, social stressors, commitment, job satisfaction, well-being, psychosomatic complaints). Changes in (multi-modally influenced) absenteeism and in the evaluation of the management?s style of leadership were not significant. Referring to the effects? impact 9 out of 12 measures proved to be positively significant in at least one criterion, whereas referring to (subjectively felt) utility all 12 measures turned out to be positively significant. In six of the remaining nine measures the cost-benefit-analysis resulted in a positive cost-benefit-relation (between 1:71 and 1:1,5). These results were critically discussed and taking into account discounting, specific result-criteria, sensitivity analyses and worst case assessment (see quality principles by Drummond, O´Brien, Stoddart &amp;amp; Torrance, 1987/1997) finally adjusted. Comparing the cost-benefit and cost-utility analyses resulted in significantly different rankings. The critical overall view allows for specific recommendations for five measure-groups. Finally, the joint discussion of the cost-benefit analysis and utility turned out to open up additional aspects of how to conduct the measures in future, which have not been described so far.